This program is designed to provide a multifaceted approach to the study of in vitro blood and cell rheology in sickle cell disease; the long range goal of the program is a better comprehension of the physiological significance of rheological and biophysical changes in sickle cell anemia and its variants. The specific aims of the present program include: 1) studies of the flow behavior of sickle erythrocyte suspensions and mixtures of normal and sickle RBC, at various oxygen tension/saturation levels, in narrow bore glass tubes having geometries relevant to the microcirculation ---such studies will allow testing of the hypothesis that reduced SS cellular deformability affects viscosity, tube hematocrit and RBC transport efficiency in small tubes and will also serve to evaluate the usefulness of a model for the prediction of small-tube viscosity; 2) studies of SS RBC microrheological correlates of intracellular hemoglobin concentration (MCHC) and oxygen tension via measurements using density-fractionated erythrocytes at various oxygen tensions, SS RBC ghosts containing differing amounts of residual hemoglobin, and sickle erythrocytes subjected to cycles of deoxygenation-reoxygenation for various cycling periods, rates and extent of deoxygenation, and in the presence of calcium channel antagonists; 3) studies of the effects of shear rate and non-S hemoglobins on the viscoelastic characteristics of HbS solutions induced to undergo gelation via a temperature-jump technique; 4) measurements of blood and RBC hemorheological alterations associated with a period of sickle cell crisis and testing of the hypothesis that WBC rheologic behavior is altered in SS disease, especially during a period of crisis. Successful completion of the major aims of this program should provide new, detailed information regarding the rheological properties of sickle blood and insight into the use of these data as supportive information for improved patient care. Of particular significance is the potential contribution which studies of this type may make to clinical medicine; although much is known about sickle hemoglobin, effective methods of treatment in this disease are still lacking. It is anticipated that the information resulting from this study may: 1) help to establish firmer criteria for the evaluation of treatment methods; 2) increase the understanding of the circulatory events which occur in sickle cell disease.